Lipase Immobilized on MCFs as Biocatalysts for Kinetic and Dynamic Kinetic Resolution of sec-Alcohols

Dominika Stradomska,Aleksandra Czernek,Nikodem Kuźnik,Katarzyna Maresz,Monika Heba,Andrzej Jarzębski,Danuta Gillner,Katarzyna Szymańska,Wojciech Pudło

doi:10.3390/catal11040518

Abstract

Dynamic kinetic resolution (DKR) is one of the most attractive methods for enantioselective synthesis. In the reported studies, lipase B from Candida antarctica (CALB) immobilized on siliceous mesoporous cellular foams (MCF) functionalized with different hydrophobic groups, and two ruthenium complexes with substituted cyclopentadienyl ligands were investigated as catalysts for the chemoenzymatic DKR of (rac)-1-phenylethanol, using Novozym 435 as a benchmark biocatalyst. Studies on the (rac)-1-phenylethanol transesterification reaction showed that CALB supported on MCFs grafted with methyl groups is a promising biocatalyst and isopropenyl acetate is a preferable acylation agent. Both Ru-complexes activated by K3PO4 or t-BuOK, proved to be effective catalysts of the racemization reaction. The final DKR experiments using all catalysts combinations singled out, gave 96% conversion, and (R)-1-phenylethyl acetate enantiomeric excess of 98% in 8 h using K3PO4 activator.

Highlights

The augmented awareness of the importance of chirality and its strong association with biological activity, critical especially for pharmaceutical, food and agricultural industries, created an immense need for development of enantiomerically pure compounds at a reduced cost [1]
In the case of mesoporous cellular foams (MCF)-Me samples, the change in SBET was strongly influenced by the concentration of the applied disilazane, in contrast to MCF-Oc and MCF-hexadecyltrimetoxysilane +85% (Hd) samples, where only slight decrease in the surface area was observed, despite doubling the concentration of the silane used
They showed that the hydrophobic groups introduced on the carrier did not exceed 3.5% w/w in the case of disilazane (MCF-3.0Me), and 5–6% w/w in the case of silanes (MCF-3.0Oc and MCF-3.0Hd)

Summary

Introduction

The augmented awareness of the importance of chirality and its strong association with biological activity, critical especially for pharmaceutical, food and agricultural industries, created an immense need for development of enantiomerically pure compounds at a reduced cost [1]. Kinetic resolution (KR), and more recently, its dynamic kinetic mode (DKR) appears to be the most effective, and, widely studied method In this context, chemoenzymatic dynamic kinetic resolution, which combines the enzyme-catalyzed kinetic resolution (KR) of racemic sec-alcohols with the in situ chemocatalytic racemization (Scheme 1), affords the desired product as a single enantiomer in up to 100% yield [5,13,14]. Formally triacylglycerol hydrolases (EC 3.1.1.3), belong to the most versatile biocatalysts applied in organic synthesis, either in hydrolysis reactions or ester synthesis (acylation reactions), in which they usually exhibit high enantioselectivity in organic solvents Their specific structure features an active center covered by a polypeptide chain (lid), which opens up under favorable conditions. For this very reason the search for stable, hydrophobic carriers for lipase is still an important issue [27]

Methods

Results

Conclusion